Is ABCC9 p.Ser2= (c.6C>T) pathogenic?

ABCC9 p.Ser2= (c.6C>T) is classified Conflicting classifications of pathogenicity in ABCC9 (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2025-12-09). Ultra-rare (popmax 0.0187%, sas); Associated with Cardiovascular phenotype.

What condition is associated with ABCC9 p.Ser2= (c.6C>T)?

ABCC9 p.Ser2= (c.6C>T) is associated with Cardiovascular phenotype, hypertrichotic osteochondrodysplasia Cantu type, dilated cardiomyopathy 1O (ClinVar).

How common is ABCC9 p.Ser2= (c.6C>T) in the general population?

ABCC9 p.Ser2= (c.6C>T) is ultra-rare (popmax 0.0187%, sas) (gnomAD).

ABCC9 p.Ser2=

c.6C>T · rs765382139 · VCV514309

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0187%, sas)

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.7	GERP -0.95, phastCons 1
Overall
CADD	6.833	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0187% South Asian · 17/90,836 alleles

Filtering AF 0.0119% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00978%

Overall 0.00112% 18/1,608,406 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0187%	5,343
Middle Eastern	0.0165%	6,060

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: ABCC9
Protein: p.Ser2=
Coding: c.6C>T
MANE Select: NM_020297
dbSNP: rs765382139
Type: single nucleotide variant
Location: chr12:21936669 (GRCh38)
Gene constraint: LOEUF 0.557 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.72

Full ABCC9 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Cardiovascular phenotype — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: hypertrichotic osteochondrodysplasia Cantu type dilated cardiomyopathy 1O

Similar variants

ABCC9 p.Ser2Asn Uncertain significance ★★ ⚠ same residue
ABCC9 p.Ser2Gly Uncertain significance ★★ ⚠ same residue
ABCC9 c.2506-1G>A Pathogenic/Likely pathogenic ★★ same condition
ABCC9 p.Arg1116Cys Pathogenic/Likely pathogenic ★★ ⚠ same condition
ABCC9 p.Arg1116His Pathogenic ★★ ⚠ same condition
ABCC9 p.Arg1154Gln Pathogenic ★★ ⚠ same condition
ABCC9 p.Arg1154Trp Pathogenic/Likely pathogenic ★★ ⚠ same condition
ABCC9 p.Gln852Ter Pathogenic/Likely pathogenic ★★ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/abcc9-p-ser2 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown